Search Results (110)

The global expansion of highly pathogenic avian influenza A (H5N1), particularly the clade 2.3.4.4b lineage, has renewed urgent concerns about its pandemic potential in the context of its ongoing panzootic expansion and increasing cross-species transmission. Despite decades of preparedness initiatives, critical technological and structural gaps persist, especially in low- and middle-income countries (LMICs), where both vaccine access and sustainable manufacturing capacity remain limited. In this perspective, we examine key lessons from past influenza pandemics and global preparedness strategies, including the Global Action Plan for Influenza Vaccines, highlighting persistent challenges related to sustainable manufacturing capacity and equitable vaccine access. Additionally, we examine the potential of messenger RNA (mRNA) vaccine platforms to address these limitations, given their rapid design, scalable manufacturing, and adaptability to emerging pathogens. Moreover, we examine the role of neuraminidase (NA) as a complementary antigen capable of broadening immune protection and reducing viral transmission. Finally, we describe recent advances in Latin America, focusing on Argentina’s participation in the mRNA Technology Transfer Programme co-led by the World Health Organization (WHO) and the Medicines Patent Pool (MPP), as a model for strengthening regional manufacturing capacity and contributing to global pandemic preparedness. Together, these elements indicate that effective H5N1 pandemic preparedness will require the integration of improved antigen design, flexible mRNA platforms, and sustainable regional manufacturing systems aligned with global procurement strategies. Full article

Attenuated total reflection time-domain spectroscopy (ATR-TDS) in the terahertz regime was employed to investigate the dielectric response of water–acetone mixtures over the full molar concentration range. The ATR configuration enabled stable measurements in a controlled and nearly closed environment, minimizing acetone evaporation and allowing reliable characterization of this highly volatile binary system. The complex dielectric function, retrieved in the 0.4–1.6 THz range, was analyzed by means of a double Cole–Cole model, which provided a more consistent description of the mixtures than a simple Debye-based approach. A strongly nonlinear dependence on composition was observed, with the highest sensitivity in the water-rich region, where even small amounts of acetone produced a marked change in both the real and imaginary parts of the dielectric function. The extracted parameters indicate that acetone primarily suppresses the slow, cooperative relaxation channel associated with the hydrogen-bond network of water, whereas the faster channel remains comparatively less affected, consistent with its more local intermolecular origin. The evolution of the Kirkwood–Fröhlich correlation factors and of the broadening parameters further supports a progressive transition from a highly correlated hydrogen-bonded liquid to a structurally heterogeneous and weakly cooperative dipolar environment. These results demonstrate that THz ATR-TDS is a sensitive tool for probing intermolecular reorganization in aqueous binary mixtures, providing a physically grounded framework for the detection of acetone and other volatile hydrogen-bond-active species in water-based systems. Full article

Accurate characterisation of blood dielectric properties is essential for data-driven biomedical sensing, yet experimental datasets are often limited to a few discrete hemoglobin (Hb) concentrations. This constraint hinders the development of robust data-driven models. To address this, the present study introduces a framework for generating synthetic blood permittivity spectra from sparse measurements. Four data-generation strategies were investigated, combining interpolation-based techniques and probabilistic models to extend Hb-dependent spectral coverage across the measured frequency range. Model performance was evaluated using Earth Mover’s Distance (EMD) for spectral similarity, Cole–Cole parameter analysis for physical consistency, variance preservation metrics, and Hb prediction using XGBoost. The results indicate that interpolation-based approaches achieve the highest reconstruction accuracy, while Conditional Bayesian principal component analysis (Conditional BPCA) produces smooth and physically consistent spectra with stable variability characteristics. Across all methods, the generated datasets maintained sufficient Hb-related information to support reliable prediction. These findings demonstrate that the proposed framework enables effective expansion of limited dielectric datasets while supporting a multi-criteria evaluation of synthetic data quality, including fidelity, variability, and predictive relevance. Full article

In the current study, the dielectric behavior of ternary mixtures composed of glycerol and water with various salt additives is investigated over a frequency range that extends from 0.5 to 20 GHz and at temperatures between 5 and 55 °C. The investigated mixtures consisted of glycerol and water with glycerol volume ratios of 20%, 40%, and 60%. To explore the salt addition’s effect on the dielectric properties, different moderate ionic strengths of glycerol–water mixtures were prepared with NaCl concentrations of 0.10, 0.20, and 0.30 M for the same glycerol volume ratios. The ion-specific effects on the dielectric properties were investigated for prepared mixtures with a 0.10 M concentration of Na₂SO₃, NaNO₃, and KCl for the 20% glycerol ratio to explore ions with different charge density and hydration tendencies. Using dielectric spectroscopy, the frequency dependence of the real (${\epsilon }^{\prime }$) and imaginary (${\epsilon }^{″}$) dielectric constants was measured, and the associated dielectric parameters were extracted using the Cole–Cole model. This study shows that increasing the salt concentration results in a slight decrease in ${\epsilon }^{\prime }$ while ${\epsilon }^{″}$ increases dramatically, especially at lower frequencies, due to enhanced DC conductivity. An isopermittivity behavior is observed in ${\epsilon }^{\prime }$ as the temperature changes across all mixtures, and it is found to be insensitive to the addition of salt, indicating that it is mainly dictated by the glycerol–water dipolar relaxation network. Among the tested mixtures is the 20% glycerol mixture with 0.10 M KCl, which exhibits the highest ${\epsilon }^{″}$ value in the low-frequency range, attributed to its relatively high DC conductivity. Additionally, the dielectric properties of mixtures with higher glycerol ratios are found to be less sensitive to the addition of salt due to their high viscosity and the higher structured solvent network, which collectively limit ionic mobility and suppress changes in dielectric response. Full article

The geomorphological characterization of coastal–marine environments is essential for environmental management and biodiversity conservation. The objective of this study was to model the geomorphological diversity of the Punta de Coles National Reserve, located in Puerto de Ilo, Moquegua, Peru, using GNSS geodetic receivers, integrating topographic and bathymetric data to continuously represent both the emerged and submerged relief. The methodology involved establishing two “C”-order geodetic control points, implementing a closed polygon with 13 vertices, conducting a topographic survey, and recording bathymetric data along coastal transects extending 1 km offshore using an echo sounder and GNSS positioning. The data were processed in a GIS environment to generate a Coastal–Marine Digital Terrain Model (CM-DTM) with metric resolution. The results showed a total area of 171.451 ha, with elevation variations ranging from sea level to 71.617 m above sea level. Distinct geomorphological units were identified, such as coastal plains (0–5% slope), hills (15–35%), and cliffs (>45%), in addition to 16 rocky islets covering 1.537 ha. In the underwater environment, the model made it possible to identify submerged terraces, slopes, and local depressions down to a depth of −115 m, revealing a continuous transition between the land and sea topography; additionally, areas with a higher susceptibility to erosion and areas of high ecological importance were identified. This study’s contribution lies in the integration of GNSS geodetic data with topobathymetric surveys, which enabled the generation of a high-precision continuous model in an area with limited prior information, establishing a scientific baseline for coastal and marine management and conservation. Full article

Background: Conventional reference intervals (RIs) are typically expressed as fixed limits and may not adequately reflect continuous biological variation across age and sex. Next-generation reference intervals (NGRIs) allow dynamic modeling of laboratory parameters across the lifespan. This study aimed to establish age- and sex-specific NGRIs for routine hematological parameters using large-scale health examination data and to evaluate their temporal stability. Methods: Health examination records were linked with laboratory data, and a relatively healthy reference population was defined based on age (18–80 years), normal body mass index, normal blood pressure, and absence of documented disease history. NGRIs were constructed using generalized additive models for location, scale, and shape (GAMLSS) with the Box–Cox Cole and Green distribution. Age-dependent percentile curves (2.5th–97.5th) were generated using bootstrap resampling (100 iterations). Temporal external validation was conducted in five independent annual cohorts (2019–2023). Results: Age- and sex-dependent distributional patterns were observed across multiple hematological parameters, particularly RBC, HGB, and HCT. Continuous percentile curves demonstrated gradual age-related trends, with more pronounced changes in females after midlife. In temporal validation cohorts, the proportion of individuals classified outside the reference intervals remained consistently below 10% across years and sexes, indicating stable performance. Conclusions: Using large-scale real-world health examination data and a flexible distributional modeling framework, we established stable age-continuous next-generation reference intervals for routine hematological parameters. The proposed approach provides a reproducible strategy for modernizing laboratory reference interval construction and supports broader implementation in population-based laboratory medicine. Full article

Background: Virus-like particles (VLPs) represent key tools for the development of vaccines due to their ability to induce a potent immune response to epitopes presented on their surface. However, the decoration of VLPs with a complete heterologous protein on the surface remains a bottleneck for clinical translation due to the complexity of manufacture. We present a novel platform, EPIclip™, for the decoration of VLPs mediated by high-affinity protein binding partners, colicin E7 (ColE7) and immunity protein 7 (Im7), within a single prokaryotic host. We evaluate this approach using a modified hepatitis B core capsid protein and IL-31 as a model epitope. IL-31 is a prominent therapeutic target for the development of pruritic diseases. Methods: We explore the design and development of the platform, including the use of T-cell-stimulating peptides. We demonstrate several small-scale purification methods for the candidate VLP, as well as morphological analysis by transmission electron microscopy (TEM). Further, we vaccinate mice with IL-31-displaying VLPs to evaluate immunogenicity and the ability to prevent IL-31-induced pruritus in vivo. Results: Our results demonstrate that decorated VLPs dosed in mice elicit an IgG response against IL-31 with at least six months of durability. In addition, IL-31-displaying VLPs suppress the development of IL-31-induced pruritus, confirming in vivo target neutralisation. Notably, IL-31-displaying VLPs induce a strong T-cell response against the VLP capsid but not against the cytokine, confirming a B-cell-biased immune response and the absence of detrimental autoreactive T cells. We further demonstrate the translation of this system with an additional virus capsid: tomato aspermy virus (TAV). Conclusions: Taken together, the novel EPIclip™ platform may represent a promising therapeutic approach for pruritic diseases. Additionally, this modular system could be adapted for a wide range of research as well as human and veterinary therapeutic applications. Full article

Cryotherapy and radiofrequency (RF) treatments modulate tissue temperature to induce therapeutic effects; however, improper application can result in thermal injury. Traditional temperature-based monitoring methods rely on multiple thermal sensors whose accuracy strongly depends on their number and spatial positioning, often failing to detect early tissue crystallization. This study introduces a fractional order bioimpedance modelling framework for the early detection of tissue freezing during cryogenic and thermal medical treatments, with the feasibility and effectiveness of this approach having been reported in our prior publications. While bioimpedance spectroscopy itself is a well-est. The corresponablished technique in biomedical engineering, its novel application to predict and identify premature freezing events provides a new pathway for safe and efficient energy-based therapies. Fractional-order models derived from the Cole family accurately reproduce the complex electrical behavior of biological tissues using fewer parameters than classical integer-order models, thus reducing both hardware requirements and computational cost. Experimental impedance data from human abdominal, gluteal, and femoral regions were modelled to extract fractional parameters that serve as sensitive indicators of phase-transition onset. The results demonstrate that the proposed approach enables real-time identification of freezing-induced electrical transitions, offering a physiologically grounded alternative to conventional temperature-based monitoring. Furthermore, the fractional order bioimpedance method exhibits high reproducibility and selectivity, and its analytical figures of merit, including the limits of detection and quantification, support its use for reliable real-time tissue monitoring and early injury detection. Overall, the proposed fractional order bioimpedance framework enhances both safety and control precision in cryogenic and thermal medical applications. Full article

Obtaining accurate estimates of the true probabilities of sporting events remains a long-standing problem in sports analytics. In this paper we propose a new domain-driven approach that infers true probabilities from betting odds. This task is not trivial, as betting odds are noisy because of bookmaker margins (vig), insider bets, and model imperfections. In this study, we present a novel approach that integrates estimates across multiple groups of betting markets to obtain more robust estimates of true probability. Our method takes market structure into account and constructs a constrained optimisation problem that is solved using the Dixon–Coles model of a football match. We compare our approach with a wide range of existing methods, using a large dataset of 359035 matches from more than 6000 leagues. The proposed method achieves the lowest log-loss and the best probability calibration among all tested approaches. It also performs the best in terms of expected profit convergence in Monte Carlo simulations, outperforming its competitors in terms of MSE and bias. This study contributes both to a new margin-removal (devig) method and provides a comprehensive comparative analysis of other known methods. Beyond football, this approach has potential applications in other sports with discrete scoring systems and potentially in other areas involving stochastic processes and market inference, such as prediction markets, finance, reliability engineering, and social prediction systems. Full article

Dielectric characterization offers valuable insights into fruit structure, ripening, and storage stability. However, systematic studies on apples are still limited. This work elucidates the electrical and physicochemical properties of a specific variety of apples, Malus domestica, using Electrochemical Impedance Spectroscopy (EIS), a non-destructive, fast and cost-effective technique, suitable for real-time quality assessments. The apple samples were analyzed over the frequency range of 20 Hz–120 MHz at 25 °C, and impedance data were modeled using equivalent circuits and dielectric relaxation models. Physicochemical analyses confirmed a high moisture content (84%, wwb), pH 4.81, TSS 14.58 °Brix, and acidity 0.64%, which is typical of fresh Red Delicious apples. Impedance spectra revealed semicircular and Warburg elements in Nyquist plots, indicating resistive, capacitive, and diffusive processes. Equivalent circuit fitting with the proposed R-C-Warburg impedance model outperformed (R² = 0.9946 and RMSE = 6.610) the classical Cole and Double-Shell models. The complex permittivity (ε) represented a frequency-dependent ionic diffusion, space-charge polarization, and dipolar relaxation decay, while electrical modulus analysis highlighted polarization and charge carrier dynamics. The translational hopping of charge carriers was confirmed through AC conductivity following Jonscher’s power law with an exponent of ƞ = 0.627. These findings establish a comprehensive dielectric profile and advanced circuit fitting for biological tissues, highlighting a promising non-invasive approach using EIS for real-time monitoring of fruit quality, with direct applications in post-harvest storage, supply chain management, and non-destructive quality assurance in the food industry. Full article

Since the first paper published by Susan Cole in 1990 detailing multidrug resistance mediated by ABCC1/MRP1, research into the C-subfamily of ATP-binding cassette transporters has continued to uncover a wide range of functionally divergent proteins. However, several orphan transporters remain in the C-subfamily, and the physiological function and substrates of ABCC5, ABCC11, and ABCC12 remain elusive. This review explores the emerging understanding of human ABCC5. Unlike other ABC transporters with well-defined drug export functions, ABCC5’s physiological roles remain only partially understood. While it is known for its involvement in multidrug resistance in cancers, recent studies suggest broader implications in development, metabolism, neurobiology, and male fertility. ABCC5 exports various endogenous substrates, including cyclic nucleotides (cAMP and cGMP), glutamate conjugates like NAAG, and possibly haem. Knockout models in mice, zebrafish, and sea urchins reveal ABCC5’s role in gut formation, brain function, eye development, and iron metabolism. In mice, its deletion results in lower adipose tissue mass, enhanced insulin sensitivity, and neurobehavioral changes resembling schizophrenia, highlighting its role in glutamatergic signalling and circadian regulation. Functionally, ABCC5 appears to impact adipocyte differentiation and GLP-1 release, implicating it in type 2 diabetes susceptibility in humans. Structural studies using human ABCC5 revealed a novel autoinhibitory mechanism involving a peptide segment (C46–S64) that blocks substrate binding, offering new potential for selective inhibitor development. However, this review emphasises caution in targeting ABCC5 for cancer therapy due to its underappreciated physiological function(s), particularly in the brain and male reproductive system. Understanding ABCC5’s substrate specificity, regulatory mechanisms, and functional redundancy with its paralog ABCC12 remains critical for successful therapeutic strategies in humans. Full article

Soil nutrient monitoring is essential to achieving UN development goals and meeting the projected 70% increase in agricultural production from 2009 values by 2050. This study presents a novel, low-cost impedimetric device for the direct and simultaneous measurement of soil ion bioavailability (Na⁺, K⁺), temperature, and humidity. Designed for Arduino integration, the device offers scalable, cost-effective deployment. Different AI algorithms were trained to interpret signals (Support Vector Machine, Random Forest, XBoost), enabling real-time monitoring. Best performance was achieved for XBoost. Calibration was first performed using solutions of known NaCl and KCl concentrations to establish impedance patterns, and benchmarking against fitted Cole model outputs demonstrated high predictive accuracy (R² = 0.99 for both Na⁺ and K⁺). The system operated across a 1–100 kHz impedance range with environmental resolution of ±0.5 °C, ±3% RH, and ±1 hPa, acquiring data every 10 min during in vivo trials. This affordable, AI-enhanced platform has the potential to empower smallholder farmers by reducing reliance on costly laboratory analyses, enabling precise fertiliser application, and integrating seamlessly into smart farming platforms for sustainable yield improvement. Full article

Jordan’s aging population faces a critical challenge: a strong cultural preference for aging at home, rooted in Islamic ethics of familial care (birr al-wālidayn), conflicts with housing stock that is largely unsafe and inaccessible. This first national mixed-methods study examines the intersection of home modifications, socio-economic barriers, and cultural constraints to aging in place. Data from 587 surveys and 35 interviews across seven governorates were analyzed using chi-square tests, linear regression, and thematic coding. Results indicate that while physical modifications significantly improve accessibility to key spaces like kitchens and reception areas (majlis) (χ² = 341.86, p < 0.001), their adoption is severely limited. Socio-economic barriers are paramount, with 34% of households unable to afford the median modification cost of over $1500. Cultural resistance is equally critical; 22% of widows avoid modifications like grab bars to prevent the ‘medicalization’ of their home, prioritizing aesthetic and symbolic integrity over safety. The study reveals a significant gendered decision-making dynamic, with men controlling 72% of structural modifications (β = 0.27, p < 0.001). We conclude that effective policy must integrate universal design with Islamic care ethics. We propose three actionable recommendations: (1) mandating universal design in building codes (aligned with SDG 11), (2) establishing means-tested subsidy programs (aligned with SDG 10), and (3) launching public awareness campaigns co-led by faith leaders to reframe modifications as preserving dignity (karama) (aligned with SDG 3). This approach provides a model for other rapidly aging Middle Eastern societies facing similar cultural-infrastructural tensions. Full article

Background: Early identification of visual disorders in children is essential to prevent long-term visual impairment and support academic development. Despite the recognized importance of visual screenings, no universal consensus exists on which visual parameters or threshold values should be used, particularly for measuring visual acuity (VA) in pediatric populations. Objectives: This study aimed to develop age-related percentile norms for VA using LEA symbol charts. Methods: A sample of Italian schoolchildren aged 5 to 15 years (n = 1510) participated in the study. Data were collected retrospectively from school-based vision screenings conducted across 12 schools in the Lombardy and Piedmont regions from 2010 to 2019. Monocular and binocular VA were measured at 3 m using a standardized LEA symbol chart, and values were scored letter-by-letter on a LogMAR scale. Smoothed percentile curves were derived using Box–Cox, Cole, and Green distribution modeling and regression analysis. Results: The results showed a non-linear improvement in VA with age. Compared to prior studies, LEA symbols yielded slightly lower VA scores, reinforcing the need for chart-specific norms. The 50th percentile VA improved from approximately +0.07 LogMAR at age 6 to about −0.09 LogMAR at age 15. Conclusions: These findings highlight the importance of age-specific, chart-specific, and statistically robust reference data for VA screening in children. The derived percentile tables offer a more sensitive tool than fixed cut-offs for identifying visual anomalies and tailoring clinical interventions. This work contributes to standardizing pediatric VA screening practices and improving early detection of visual deficits. Full article

The frequency-domain controlled-source electromagnetic method (CSEM) has been widely used in fields such as oil and gas and mineral resource exploration. In areas with a significant IP response, the CSEM signals will be modified by the IP response of the subsurface. Accurately extracting resistivity and polarization information from CSEM signals may significantly improve the exploration interpretations. In this study, we replaced real resistivity with the Cole–Cole complex resistivity model in a forward simulation of the CSEM to obtain electric field responses that included both induced polarization and electromagnetic effects. Based on this, we used the adaptive differential evolution algorithm to perform a 1-d inversion of these data to extract both the resistivity and IP parameters. Inversion of the electric field responses from representative three-layer geoelectric models, as well as from a more realistic seven-layer model, showed that the inversions were able to effectively recover resistivity and polarization information from the modeled responses, validating our methodology. The electric field response of the real geoelectric model, with 20% random noise added, was then used to simulate actual measured CSEM signals, as well as subjected to multiple inversion tests. The results of these tests continued to accurately reflect the resistivity and polarization information of the model, confirming the applicability and reliability of the algorithm. These results have significant implications for the processing and interpretation of CSEM data when induced polarization effects merit consideration and are expected to promote the use of the CSEM in more fields. Full article